Recently, we discovered that the bacterial receptor for FimH-expressing bacteria was localized in plasmalemmal caveolae of mast cells and that these caveolae were actively involved in the internalization of the bacteria. Caveolae are subcellular entities rich in glycolipid; and cholesterol and typically contain the scaffolding protein, caveolin. Caveolae mediated bacterial uptake is remarkable because intracellular bacteria remain viable and encased in membranes comprising of caveolar components. Although the significance and scope of caveolae-mediated bacterial uptake by mast cells is, as yet, unknown, this observation represents a novel activity for cellular caveolae in immune cells. To extend our observations, the following specific aims are proposed: (I), Define the scope and molecular basis for caveolae-mediated uptake of bacteria (II), Elucidate the ultimate fate of bacteria internalized via caveolae and (III), Investigate the molecular basis for the caveolae-mediated uptake of FimH-expressing bacteria in human mast cells. Our observations highlighting the role of cellular caveolae in the uptake of bacteria represents an important and novel activity triggered by pathogens in immune cells. The proposed studies should provide new insights into the cellular response of mast cells and possibly other immune cells to infectious agents and provide new clues for devising effective strategies to combat bacterial infections.